DESCRIPTION (Applicant's abstract): Our long term goal is to obtain an understanding of the role of bound inositol-(1,4,5) trisphosphate (Ins(1,4,5)P3) in airway smooth muscle. Studies have established that Ins(-1,4,5)P3 is bound to purified porcine trachealis smooth muscle (PTSM) aldolase C and that there is a large cellular content of aldolase C in this muscle. Our data suggest that if Ins(1,4,5)P3 bound to aldolase C in intact muscle were rapidly and completely released, this could increase cytosolic free (Ins(1,4,5)P3) to and above threshold levels for Ca2+ release. Ins(1,3,4)P3 and aldolase substrate Fru(1,6)P2 released aldolase C-bound Ins(1,4,5)P3. A high affinity for Ins(1,4,5)P3 binding to aldolase C complexed to cytoskeletal actin suggests there is a large cytoskeleton bound Ins(1,4,5)P3 store and supports a physiological role of cytoskeletal actin bound Ins(1,4,5)P3. We will test the hypothesis that Ins(1,3,4)P3-evoked release of Ins(1,4,5)P3 from binding sites on cytoskeleton aldolase-actin functions to amplify and regenerate phospholipase C produced Ins(1,4,5)P3-induced sarcoplasmic reticulum Ca2+ release in agonist-stimulated intact muscle.